title: A novel tetrapeptide derivative exhibits in vitro inhibition of neutrophil-derived reactive oxygen species and lysosomal enzymes release.
abstract: Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39-42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.
authors.affiliation: Department of Biotechnology, Central Leather Research Institute, Chennai 600020, India. smiriy@lsuhsc.edu
authors.forename: Sumitra
authors.initials: S
authors.lastname: Miriyala
authors.forename: Manikandan
authors.initials: M
authors.lastname: Panchatcharam
authors.forename: Meera
authors.initials: M
authors.lastname: Ramanujam
authors.forename: Rengarajulu
authors.initials: R
authors.lastname: Puvanakrishnan
mesh_terms: D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism; D003720:Densitometry; D005260:Female; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D009203:Myocardial Infarction / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D017382:Reactive Oxygen Species; D003165:Complement System Proteins